CN106139255A - A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate - Google Patents

A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate Download PDF

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Publication number
CN106139255A
CN106139255A CN201510193633.3A CN201510193633A CN106139255A CN 106139255 A CN106139255 A CN 106139255A CN 201510193633 A CN201510193633 A CN 201510193633A CN 106139255 A CN106139255 A CN 106139255A
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China
Prior art keywords
calcium phosphate
collagen
tcp
mesh
collagen protein
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CN201510193633.3A
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毕宏伟
杜宪明
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TIANJIN SANNIE BIOENGINEERING TECHNOLOGY Co Ltd
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TIANJIN SANNIE BIOENGINEERING TECHNOLOGY Co Ltd
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Priority to CN201510193633.3A priority Critical patent/CN106139255A/en
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Abstract

The present invention is new material and the preparation method of a kind of medical sponge support as raw material with collagen protein and calcium phosphate.The present invention describes a kind of collagen protein and combines the new material of medical sponge support and the preparation method of calcium phosphate.Belong to biological medicine Material Field.When mainly solving to treat osteocartilaginous and subchondralo bone injury at present, can not carry out cartilaginous tissue reparation and problem that cartilaginous tissue to be repaired connected bone densification position (i.e. os osseum position) merges, the bone renovating material overcoming the most clinical collagen protein/calcium phosphate can not repair the phenomenon of osteochondral tissue damage well simultaneously.

Description

A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate
Technical field
The present invention relates to a kind of collagen protein and combine the new material of medical sponge support and preparation method, the glue of preparation of calcium phosphate Olynthus support can be used for repairing the damage of osteochondral tissue.
Background technology
Disease or wound can cause the cartilage layers (also known as bone cartilage) of people's skeleton to be damaged, and clinic can be similar to cartilage by implantation Substitute, for repairing or the cartilaginous tissue of regeneration of damaged wound, especially has the collagen protein of biocompatibility and biological degradability. Collagen protein can induce the cell promoting blood vessel and nervous tissue's growth to adhere at cartilaginous lesion site as support, migrates and grows, entering And promote the regeneration of cartilaginous tissue.Calcium phosphate is the host inorganic phase chemical composition of osseous tissue, particularly hydroxyapatite (chemistry point Minor Ca5(PO4)3OH, English hydroxyapatite, write a Chinese character in simplified form HA) and bata-tricalcium phosphate (chemical molecular formula Ca3(PO4)2, English β -tricalcium phosphate, writes a Chinese character in simplified form β-TCP) it is the height similar substance of osseous tissue composition, porosity is similar to bone sponge very much Shape tissue, has the performance of good bone conduction and self-bone grafting, and therefore by HA, or β-TCP, or HA and β-TCP mixture (is write a Chinese character in simplified form HA/ β-TCP), and collagen protein is used in mixed way the reparation for bone injury.The collagen protein of Clinical practice combines calcium phosphate at present The bone repairing support of (writing a Chinese character in simplified form collagen/calcium phosphate), has good bone compact part repair, but is difficult to owing to hardness is higher moulding And be not suitable for repairing cartilage and include osseocartilaginous damage.For overcoming this problem, by adding certain grain in collagen matrices HA or β-TCP or the HA/ β-TCP of footpath and certain content is prepared as the sponge bracket of semi-solid, it is achieved one end hardness is high like solid Body can stick bone compact part, and other end elasticity can fill up the damage space of cartilage like sponge, has so simultaneously facilitated osseocartilaginous Regeneration and the fusion with bone compact part.
Summary of the invention
It is an object of the present invention to provide and a kind of there is good bio-compatible performance, biodegradability and osteochondral tissue repairing performance The sponge bracket preparation method of semi-solid of collagen/calcium phosphate, for treating the damage of osteochondral tissue.Its step is as follows:
(1) with the molecular sieve mesh screen of suitable mesh selected from system or commercially available HA or β-TCP, < 0.1mm (150 is obtained Mesh), 0.1-0.3mm (between 150 mesh and 50 mesh) and the powder of > 0.3mm (50 mesh) three groups of different-grain diameters or granule.If With HA/ β-TCP, in specific weight ratio (optional any ratio between 80%: 20% to 20%: 80%), screening is obtained Both same particle size are homogenously mixed together.
(2) in a container, weigh self-control or commercially available collagen protein, join injection pure water, arrive with acetic acid regulation pH value 3.0-4.5, is prepared as the suspension of 1-1.5% collagen solution (w/v, w/v), be divided into that volume is identical four parts.Vacuum is taken out Rate removes bubble removing.
(3) calcium phosphate powder of each particle diameter above-mentioned or granule are individually added in the way of weight ratio (w/w) a collagen molten In liquid, the agitation of agitator low speed forms suspension, more some hours of prolonged agitation is until being swelled into colloid, obtains accounting for collagen/calcium phosphate Gross weight ratio is respectively three kinds of colloid solution of 15% (< 0.1mm HA), 45% (0.1-0.3mm HA) and 75% (> 0.3mm HA).
(4) by the colloid solution containing different-grain diameter calcium phosphate according to particle diameter order from big to small, one layer cover one layer on side Formula is evenly laid out in a reservoir, topmost adds the 1-1.5% collagen solution without calcium phosphate.
(5) due to the collagen colloid solution very thickness of 1-1.5%, will not quickly merge between every layer, before fusion by container in -20 DEG C of rapid cooled and solidified become solid.
(6) vacuum lyophilization obtains the sponge bracket of semi-solid, and apparent high for one end hardness, one end elasticity is high.
(7) sponge bracket is placed in the cross-linking agent solutions such as glutaraldehyde immersion, takes out and air-dry.
(8) sponge bracket cutting into required size, packaging, gamma-ray irradiation is degerming makes end product.
Detailed description of the invention
Example one
Weigh 15g collagen powder, add 1000ml injection pure water and dissolve the solution being made into 1.5%, with acetic acid regulation pH value be 3.8.By volume it is divided into quarter.Vacuum pumping rate removes bubble removing.In first part, add particle diameter < 0.1mm HA reach to account for collagen/HA The 15% of weight ratio, second part adds particle diameter 0.1-0.3mm HA and reaches to account for the 45% of collagen/HA weight ratio, and second part adds grain Footpath > 0.3mm HA reaches to account for the 75% of collagen/HA weight ratio.Agitator stirs with 500rpm speed low speed until being formed uniform HA suspension, prolonged agitation is allowed to be swelled into colloid for some hours.The collagen containing particle diameter > 0.3mm HA is poured gently in a container / HA colloid, pours the collagen containing particle diameter 0.1-0.3mm HA/HA colloid into, the most gently successively containing particle diameter < 0.1mm HA Collagen/HA colloid, and the collagen solution without HA.Container is put into-20 DEG C is frozen into solid rapidly.Vacuum lyophilization obtains The collagen sponge scaffold of semi-solid, apparent high for one end hardness, one end elasticity is high.Sponge bracket is placed in the cross-linking agent such as glutaraldehyde Solution soaks, takes out and air-dry;Sponge bracket cuts into required size, and packaging, gamma-ray irradiation is degerming makes end product.

Claims (1)

1. it is used for making collagen protein and combines the new material of medical sponge support and the preparation method of calcium phosphate (collagen/calcium phosphate), Product is used for treating osseocartilaginous damage tissue, and calcium phosphate kind can be hydroxyapatite (HA) or bata-tricalcium phosphate (β-TCP) Or the mixture (HA/ β-TCP) of hydroxyapatite and bata-tricalcium phosphate, select including by HA or β-TCP molecular sieve mesh screen Obtaining powder or the granule of < tri-kinds of particle diameters of 0.1mm, 0.1-0.3mm and > 0.3mm, the collagen solution being added separately to 1-1.5% is made into HA or β-TCP accounts for collagen/calcium phosphate gross weight than respectively 15% (< 0.1mm), 45% (0.1-0.3mm) and 75% (> 0.3mm) The colloid solution of collagen/calcium phosphate, according to calcium phosphate powder or the size of granule, one layer cover one layer on mode by upper State colloid solution be laid in make sponge bracket container in, if with HA/ β-TCP, the HA of the same particle size that screening is obtained with β-TCP mixes equably, and both weight ratios can be any ratio between 80%: 20% to 20%: 80%, it is characterised in that system Standby process includes following each step:
(1) take from system or commercially available HA or β-TCP screening obtain < 0.1mm (150 mesh), 0.1-0.3mm (150 mesh and 50 mesh it Between) and the powder of > 0.3mm (50 mesh) three kinds of particle diameters or granule;If with HA/ β-TCP, weight ratio in specific proportions (can Select any ratio between 80%: 20% to 20%: 80%), both same particle size screening obtained are homogenously mixed together;
(2) by the HA of three kinds of particle diameters, or β-TCP, or HA/ β-TCP powder or granule are separately added to the collagen solution of a 1-1.5% In, the agitation of agitator low speed forms suspension, and prolonged agitation obtains accounting for gross weight ratio respectively for some hours until being swelled into colloid It is 15% (< 0.1mm), three kinds of colloid solution of 45% (0.1-0.3mm) and 75% (> 0.3mm);
(3) by the above-mentioned collagen colloid solution containing different-grain diameter calcium phosphate according to particle diameter order from big to small, one layer cover one layer on Mode evenly laid out in a reservoir, topmost add the collagen solution of the 1-1.5% without calcium phosphate, be placed in-20 DEG C of refrigerators immediately It is cooled to solid;
(4) vacuum lyophilization obtains the sponge bracket of collagen/calcium phosphate, and one end hardness High Availabitity is in sticking bone compact part, and one end is elastic High Availabitity is in filling up osteocartilaginous and subchondralo bone injury position.
CN201510193633.3A 2015-04-17 2015-04-17 A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate Pending CN106139255A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106729986A (en) * 2016-12-28 2017-05-31 上海市第六人民医院 Mix the preparation method of zinc calcium phosphate microsphere collagen composite biomimetic scaffolds
CN114425104A (en) * 2021-12-21 2022-05-03 中国人民解放军空军军医大学 Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof
EP4382141A1 (en) 2022-12-05 2024-06-12 Ustav materialoveho vyskumu Slovenskej Akademie vied, verejna vyskumna institucia Composite biocement system

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1207753A (en) * 1995-11-09 1999-02-10 威廉·邦菲尔德 Bioactive composite material for repair of hard and soft tissues
CN1943801A (en) * 2006-11-01 2007-04-11 华中科技大学 A gradient laminated composite supporting frame material based on bionic structures and its preparation method
CN101163512A (en) * 2005-03-04 2008-04-16 法恩扎Fin-陶瓷股份公司 Cartilaginiform and osteochondral sustitute comprising a multilayer structure and use thereof
CN101628131A (en) * 2009-08-25 2010-01-20 华中科技大学 Method for preparing ultra-thin porous lamination gradient composite support of tissue engineering
CN102294052A (en) * 2011-07-27 2011-12-28 东南大学 Preparation method of medical high polymer based silver nano material

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1207753A (en) * 1995-11-09 1999-02-10 威廉·邦菲尔德 Bioactive composite material for repair of hard and soft tissues
CN101163512A (en) * 2005-03-04 2008-04-16 法恩扎Fin-陶瓷股份公司 Cartilaginiform and osteochondral sustitute comprising a multilayer structure and use thereof
CN1943801A (en) * 2006-11-01 2007-04-11 华中科技大学 A gradient laminated composite supporting frame material based on bionic structures and its preparation method
CN101628131A (en) * 2009-08-25 2010-01-20 华中科技大学 Method for preparing ultra-thin porous lamination gradient composite support of tissue engineering
CN102294052A (en) * 2011-07-27 2011-12-28 东南大学 Preparation method of medical high polymer based silver nano material

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106729986A (en) * 2016-12-28 2017-05-31 上海市第六人民医院 Mix the preparation method of zinc calcium phosphate microsphere collagen composite biomimetic scaffolds
CN114425104A (en) * 2021-12-21 2022-05-03 中国人民解放军空军军医大学 Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof
CN114425104B (en) * 2021-12-21 2023-03-03 中国人民解放军空军军医大学 Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof
EP4382141A1 (en) 2022-12-05 2024-06-12 Ustav materialoveho vyskumu Slovenskej Akademie vied, verejna vyskumna institucia Composite biocement system

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